The objectives of this proposal are to study the role of bacterial adherence to the trachea in the pathogenesis of pulmonary infections, and to determine whether various inhibitors of adherence can be developed to prevent pulmonary infections. We suggest, that because aspiration is a major means by which humans develop pneumonia, adherence to the tracheobronchial tree is an important step in enabling bacteria to overcome the mucociliary apparatus. We hypothesize, that aspirated bacteria adhere to the cells of a damaged tracheobronchial tree, multiply to larger numbers, and are then aspirated either attached to a desquamating cell or by themselves. We have observed that following influenza virus infections of mice, Pseudomonas aeruginosa adheres to desquamating cells, Staphylococcus aureus to remaining ciliated cells and Streptococcus pneumoniae to regenerating cells, and that following endotracheal intubation of ferrets, Pseudomolas aeruginosa adheres to desquamating cells. We, therefore, propose to study the adherence of bacteria to the trachea under several conditions that damage the trachea, (1) after influenza infections of mice, (2) following endotracheal intubation of ferrets, (3) after cytotoxic chemotherapy and irradiation treatment of mice, and (4) following aspiration of gastric juice and/or saliva in mice to produce tracheal damage. We will also test the hypothesis that bacteria attached to aspirated cells will cause pneumonia and then further proceed to find inhibitors of bacterial adherence using synthetic biopolymers or simple sugars. We propose to use these to prevent pneumonias in animal models under conditions of tracheal damage.